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Endoscopic near infrared and indocyanine green to verify the viability of the subcutaneous flap for vulvar cancer.

2019

Abstract Introduction Vulvar cancer often requires radical vulvectomy with subsequent vulvar flap. Approximately in 20–60% of cases, there are post-operative complications ranging from infection to flap necrosis that often require reoperation. Several methods have been described to verify the vitality of the flap, but these are often expensive and require specific machinery that is not generally present in a gynecological clinic. In this case report, we present a viability verification of V Y fasciocutaneous advancement flap for vulvar reconstruction by Endoscopic Near-Infrared and Indocyanine Green. Methodology The patient was a 67-year-old woman with FIGO IB ≤ 4 cm squamous cell vulvar ca…

Targeting RNA structure in SMN2 reverses spinal muscular atrophy molecular phenotypes

2018

Modification of SMN2 exon 7 (E7) splicing is a validated therapeutic strategy against spinal muscular atrophy (SMA). However, a target-based approach to identify small-molecule E7 splicing modifiers has not been attempted, which could reveal novel therapies with improved mechanistic insight. Here, we chose as a target the stem-loop RNA structure TSL2, which overlaps with the 5′ splicing site of E7. A small-molecule TSL2-binding compound, homocarbonyltopsentin (PK4C9), was identified that increases E7 splicing to therapeutic levels and rescues downstream molecular alterations in SMA cells. High-resolution NMR combined with molecular modelling revealed that PK4C9 binds to pentaloop conformati…

2021

To efficiently lower virus infectivity and combat virus epidemics or pandemics, it is important to discover broadly acting antivirals. Here, we investigated two naturally occurring polyphenols, Epigallocatechin gallate (EGCG) and Resveratrol (RES), and polyphenol-functionalized nanoparticles for their antiviral efficacy. Concentrations in the low micromolar range permanently inhibited the infectivity of high doses of enteroviruses (107 PFU/mL). Sucrose gradient separation of radiolabeled viruses, dynamic light scattering, transmission electron microscopic imaging and an in-house developed real-time fluorescence assay revealed that polyphenols prevented infection mainly through clustering of…

In Silico Insights towards the Identification of NLRP3 Druggable Hot Spots

2019

NLRP3 (NOD-like receptor family, pyrin domain-containing protein 3) activation has been linked to several chronic pathologies, including atherosclerosis, type-II diabetes, fibrosis, rheumatoid arthritis, and Alzheimer’s disease. Therefore, NLRP3 represents an appealing target for the development of innovative therapeutic approaches. A few companies are currently working on the discovery of selective modulators of NLRP3 inflammasome. Unfortunately, limited structural data are available for this target. To date, MCC950 represents one of the most promising noncovalent NLRP3 inhibitors. Recently, a possible region for the binding of MCC950 to the NLRP3 protein was described but no details were …

Subcutaneous injection of exosomes reduces symptom severity and mortality induced by Echinostoma caproni infection in BALB/c mice.

2016

Recent studies have shown the importance of exosomes in the host-parasite relationship. These vesicles are an important part of the excretory/secretory pathway for proteins with the potential to alter immune responses. Therefore, in the present study, we examined the immunomodulatory role of exosomes in BALB/c mice using Echinostoma caproni as an experimental model of intestinal helminth infection. For this purpose, BALB/c mice were injected twice s.c. with purified exosomes of E. caproni, followed by experimental infection. We report a delay in the development of the parasite in mice immunised with exosomes, a concomitant reduced symptom severity and increased survival upon infection. Immu…

The cotton stainer's gut microbiota suppresses infection of a cotransmitted trypanosomatid parasite

2018

The evolutionary and ecological success of many insects is attributed to mutualistic partnerships with bacteria that confer hosts with novel traits including food digestion, nutrient supplementation, detoxification of harmful compounds and defence against natural enemies. Dysdercus fasciatus firebugs (Hemiptera: Pyrrhocoridae), commonly known as cotton stainers, possess a simple but distinctive gut bacterial community including B vitamin-supplementing Coriobacteriaceae symbionts. In addition, their guts are often infested with the intestinal trypanosomatid parasite Leptomonas pyrrhocoris (Kinetoplastida: Trypanosomatidae). In this study, using experimental bioassays and fluorescence in situ…

Longitudinal study of DNA methylation during the first 5 years of life

2016

[Background]: Early life epigenetic programming influences adult health outcomes. Moreover, DNA methylation levels have been found to change more rapidly during the first years of life. Our aim was the identification and characterization of the CpG sites that are modified with time during the first years of life. We hypothesize that these DNA methylation changes would lead to the detection of genes that might be epigenetically modulated by environmental factors during early childhood and which, if disturbed, might contribute to susceptibility to diseases later in life. [Methods]: The study of the DNA methylation pattern of 485577 CpG sites was performed on 30 blood samples from 15 subjects,…

Negatively Charged Gangliosides Promote Membrane Association of Amphipathic Neurotransmitters

2018

Lipophilic neurotransmitters (NTs) such as dopamine are chemical messengers enabling neurotransmission by adhering onto the extracellular surface of the post-synaptic membrane in a synapse, followed by binding to their receptors. Previous studies have shown that the strength of the NT-membrane association is dependent on the lipid composition of the membrane. Negatively charged lipids such as phosphatidylserine, phosphatidylglycerol, and phosphatidic acid have been indicated to promote NT-membrane binding, however these anionic lipids reside almost exclusively in the intracellular leaflet of the post-synaptic membrane instead of the extracellular leaflet facing the synaptic cleft. Meanwhile…

miR-128 Is Implicated in Stress Responses by Targeting MAFG in Skeletal Muscle Cells.

2017

MAFG (v-Maf avian musculoaponeurotic fibrosarcoma oncogene homolog G) is a bZIP-type transcriptional regulator that belongs to the small MAF (sMAFs) protein family. By interacting with other bZIP transcription factors, sMAFs can form homo- and heterodimers governing either repressive or activating transcriptional functions. As heterodimeric partner of Nrf2, MAFG positively influences the ARE-dependent antioxidant/xenobiotic pathways, at least in condition of a correct MAFG:Nrf2 balance. MicroRNAs (miRs) participate to different regulatory networks being involved as fine-tuning regulators of gene expression. However, the connections between cellular surveillance to stresses mediated by MAFG:…

Shared DNA methylation signatures in childhood allergy: The MeDALL study

2021

Contains fulltext : 232514.pdf (Publisher’s version ) (Open Access) BACKGROUND: Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema. OBJECTIVE: We sought to identify DNA methylation profiles associated with childhood allergy. METHODS: Within the European Mechanisms of the Development of Allergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation by using a cross-sectional design. Allergy was defined as having symptoms from at least 1 allergic disease (asthma, rhinitis, or eczema) and positive serum-specific IgE to common aeroallergens. The discove…